Neuronal diseases can be debilitating conditions that involve the malfunction, deterioration, or death of neurons. For example, when a person suffers from a neurodegenerative disease, his or her neurons deteriorate, which can initially manifest as forgetfulness, cognitive impairment, or loss of coordination. As the disease progresses, the person's condition can worsen considerably and he or she may become unable to walk and may suffer from severe dementia. Neurodegenerative diseases often present no outwardly visible symptoms until after they have caused significant harm to the nervous system.
Some neurodegenerative diseases are known to be associated with certain mutations or combinations of mutations. For example, variants of genes such as C9orf72, SOD1, TARDBP, FUS, UBQL2, ALS2, and SETX are known to be associated with amyotrophic lateral sclerosis or other neural disorders and the progression of the disease can vary depending on what combination of variants are present in a patient's genome. See Finsterer & Burgunder, 2014. Recent progress in the genetics of motor neuron disease. Eur J Med Genet, In press. As a consequence, simply by knowing that a person has one disease-associated mutation (e.g., C9orf72), a clinician cannot conclude that a disorder will manifest in that person. Furthermore, distinct underlying causes of a disease, for instance due to different mutations or due to differences in genetic background, may lead to outwardly similar sets of symptoms. Nonetheless, the treatment may need to be tailored to the underlying root-cause of the disease and to the particularities of each patient's genetic background.
Two factors conspire to prevent patient classification based solely upon genetic information: First, due to the vast number of possible disease-causing mutations, many such mutations occur at a very low level in the population. Additionally, there is a high level of genetic variation in the population that is not directly associated with disease. Thus from sequence alone, a clinician may not be able to determine which mutations are causative in a disease. Even if the mutation is found, the number of comparable cases may be so small that data on optimal treatment strategies is lacking.